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Optimal Anemia Treatment in End Stage Renal Disease (ERSD)
Conditions
Hyperparathyroidism, Secondary
Conditions: official terms
Hyperparathyroidism - Hyperparathyroidism, Secondary - Kidney Failure, Chronic - Neoplasm Metastasis
Conditions: Keywords
Hyperparathyroidism, Secondary, Anemia, Vascular Stiffness, Vascular Calcification
Study Type
Interventional
Study Phase
N/A
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Intervention
Name: standard care
Type: Drug
Name: Optimal (I. iPTH control: Zemplar®,Mimpara®; phosphorous control: Renvela®, Phoslo®, Osvaren®, Foznol®,Maalox®; calcium control: calcium and vitamin D
Type: Drug
Overall Status
Not yet recruiting
Summary
Clinical study aimed at improving anemia management in End Stage Renal Disease Patient (ESRD) on maintenance Hemodialysis with evidence of Chronic Kidney disease Mineral Bone Disorder (CKD-MBD)
Detailed Description
Anemia is one of the most worrisome complications of Chronic Kidney Disease (CKD). Numerous prospective studies have repeatedly documented an increase risk of morbidity and mortality associated with lower levels of hemoglobin (Hb). Hence the international guidelines on patient care suggest the use of Erythropoietin Stimulating Agents (ESA), iron, folates supplementation for anemia correction.
However, recent randomized controlled trials (RCT) have demonstrated that hemoglobin correction to normal levels increases the risk of major cardiovascular (CV) events. Though, the reasons are still unclear, the cumulative ESA dose may at least partly explain these findings suggesting limiting ESA to the minimal dose allowed to achieve the suggested Hb targets in ESRD patients.
Among other factors, CKD-MBD has been repeatedly associated with poor more severe anemia and higher dose of ESA. However, the latest Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on CKD-MBD management suggest a higher reference target for intact parathyroid hormone (iPTH) (2-9 fold the upper level of the normal range) when compared to the National Kidney Foundation (NKF) guidelines published in 2003 (150-300 pg/ml).
A few observational studies suggest a linear inverse association between intact iPTH and ESA dose even for iPTH value within the iPTH target level proposed by the KDIGO working group. Similarly, a large body of evidence supports the notion that the higher the iPTH the faster the CV system deterioration in ESRD.
Aim of the study is to test whether a tighter iPTH control to achieve a iPTH level lower than 300 pg/ml vs iPTH levels between 300-540 pg/ml is associated with a ESA dose reduction and a slower CV system deterioration in ESRD patients receiving dialysis.
STUDY DESIGN Pilot, single center, open label with blinded end point (PROBE-Prospective Randomized Open Blinded End-Point) aimed at improving patient care.
Eligible patients will be randomized (1:1) to either:
(A) Control group: standard care. The iPTH target in this group is 300-540 pg/ml (B) Optimal CKD-MBD control: in this group the iPTH target is150-300 pg/ml to be achieved with a therapeutic algorithm.
TREATMENTS
All patients will be randomized (1:1) to either:
(A) Control group: standard care. The iPTH target in this group is 300-540 pg/ml.
(B) Optimal CKD-MBD control:: in this group the iPTH target is 150-300 pg/ml to be achieved with a therapeutic algorithm:
I. iPTH control: in order to achieve the iPTH target (150-300 pg/ml), all patients will receive 400 IU/day of vitamin-25-OH-D (25OHD) and a flexible dose of any active vitamin D available in Italy (calcitriol and paricalcitol-"Zemplar®") at the maximum dose of 6 mcg/week of paricalcitol("Zemplar®")of equivalent (see existing conversion table). Patients will also receive a flexible dose of cinacalcet("Mimpara®") to a maximum dose of 90 mg/day.
II. Phosphorous control: all patients need to achieve a serum phosphorous level lower than 5.5 mg/dl. All available phosphate binders are allowed [sevelamer("Renvela®"), calcium carbonate, calcium acetate("Phoslo®"), calcium acetate/magnesium carbonate ("Osvaren®"), lanthanum carbonate "Foznol®"). A rescue therapy with aluminum("Maalox®") is allowed for no more than 30 days.
III. Serum calcium control: the suggested target is less than 9.5 mg/dl. In case of serum calcium greater than 9.5 mg/dl the calcium and vitamin D dose should be lowered in order to lower the risk of vascular calcification deposition and progression
However, recent randomized controlled trials (RCT) have demonstrated that hemoglobin correction to normal levels increases the risk of major cardiovascular (CV) events. Though, the reasons are still unclear, the cumulative ESA dose may at least partly explain these findings suggesting limiting ESA to the minimal dose allowed to achieve the suggested Hb targets in ESRD patients.
Among other factors, CKD-MBD has been repeatedly associated with poor more severe anemia and higher dose of ESA. However, the latest Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on CKD-MBD management suggest a higher reference target for intact parathyroid hormone (iPTH) (2-9 fold the upper level of the normal range) when compared to the National Kidney Foundation (NKF) guidelines published in 2003 (150-300 pg/ml).
A few observational studies suggest a linear inverse association between intact iPTH and ESA dose even for iPTH value within the iPTH target level proposed by the KDIGO working group. Similarly, a large body of evidence supports the notion that the higher the iPTH the faster the CV system deterioration in ESRD.
Aim of the study is to test whether a tighter iPTH control to achieve a iPTH level lower than 300 pg/ml vs iPTH levels between 300-540 pg/ml is associated with a ESA dose reduction and a slower CV system deterioration in ESRD patients receiving dialysis.
STUDY DESIGN Pilot, single center, open label with blinded end point (PROBE-Prospective Randomized Open Blinded End-Point) aimed at improving patient care.
Eligible patients will be randomized (1:1) to either:
(A) Control group: standard care. The iPTH target in this group is 300-540 pg/ml (B) Optimal CKD-MBD control: in this group the iPTH target is150-300 pg/ml to be achieved with a therapeutic algorithm.
TREATMENTS
All patients will be randomized (1:1) to either:
(A) Control group: standard care. The iPTH target in this group is 300-540 pg/ml.
(B) Optimal CKD-MBD control:: in this group the iPTH target is 150-300 pg/ml to be achieved with a therapeutic algorithm:
I. iPTH control: in order to achieve the iPTH target (150-300 pg/ml), all patients will receive 400 IU/day of vitamin-25-OH-D (25OHD) and a flexible dose of any active vitamin D available in Italy (calcitriol and paricalcitol-"Zemplar®") at the maximum dose of 6 mcg/week of paricalcitol("Zemplar®")of equivalent (see existing conversion table). Patients will also receive a flexible dose of cinacalcet("Mimpara®") to a maximum dose of 90 mg/day.
II. Phosphorous control: all patients need to achieve a serum phosphorous level lower than 5.5 mg/dl. All available phosphate binders are allowed [sevelamer("Renvela®"), calcium carbonate, calcium acetate("Phoslo®"), calcium acetate/magnesium carbonate ("Osvaren®"), lanthanum carbonate "Foznol®"). A rescue therapy with aluminum("Maalox®") is allowed for no more than 30 days.
III. Serum calcium control: the suggested target is less than 9.5 mg/dl. In case of serum calcium greater than 9.5 mg/dl the calcium and vitamin D dose should be lowered in order to lower the risk of vascular calcification deposition and progression
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: INCLUSION CRITERIA.
- Men and women
- Age >18 years
- Maintenance dialysis via Artero-Venous fistula
- ESA use
- iPTH between 300-600 pg/ml
- Hb between 10.0-11.5
- Kt/V greater/equal than 1.2
- Signed informed consent prior to the initiation of the study
EXCLUSION CRITERIA: None.
- Men and women
- Age >18 years
- Maintenance dialysis via Artero-Venous fistula
- ESA use
- iPTH between 300-600 pg/ml
- Hb between 10.0-11.5
- Kt/V greater/equal than 1.2
- Signed informed consent prior to the initiation of the study
EXCLUSION CRITERIA: None.
Location
Azienda Ospedaliera Sant'Anna
San Fermo della battaglia (CO), Italy
Status: Not yet recruiting
Contact: Simona Urbano - +39.031.585.8947 - comitato.etica@hsacomo.org
Start Date
November 2014
Completion Date
October 2016
Sponsors
Azienda Ospedaliera Sant'Anna
Source
Azienda Ospedaliera Sant'Anna
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page